Animal Biotechnology is the spectrum of technologies – ranging from assisted reproductive technologies to genetic engineering and gene editing, to stem cell technology –currently being used in animals as tools for enhancing food production, for biomedical uses in human and veterinary medicine, and for basic research in disease processes. Much of CVM’s effort in this area is related to genetically engineered (GE) animals. In general, GE animals are produced by the introduction of new or altered DNA via the techniques of modern molecular biology, including recombinant DNA technology, to exhibit new or altered traits. CVM regulates these resulting animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act because the regulated article, i.e., the introduced DNA, that is intended to alter the structure or function of the animals, meets the definition of a drug.
There are many reasons for producing GE animals, including improvement of food security; reduction of diseases in animals; production of products that can be used as drugs, biologics, medical devices, food additives or other high value products; and use of large animals as models of human disease. With respect to the latter, there are often underlying reasons why large animal species such as pigs, goats, or cattle may serve as better animal models for human disease than do laboratory species, such as mice or rats. Specifically, genetically engineered pigs may serve as more biologically relevant models of human diseases (such as cystic fibrosis or Huntington’s disease) than GE or non-GE mice because their physiology more closely resembles that of humans.
The Animal Biotechnology Interdisciplinary Group (ABIG) is the nucleus of the development and implementation of CVM policies to regulate these animals. In FY 2012, ABIG continued to address challenges associated with scientific and regulatory review and policy development associated with animal biotechnology. The Group accomplished this in a team-based, matrix-managed approach to the entire life cycle with respect to products of animal biotechnology. The “life cycle” stretches from the first research and early product development, through approval, to post-approval surveillance and compliance.
ABIG consisted of 10 core members at the end of the fiscal year, supplemented by numerous associates (from CVM, other FDA Centers, and other government agencies) who are added to the effort in a novel, matrixing, approach that cuts across traditional vertical administrative structures. Matrixing allows for multi-disciplinary review teams with the membership based on the expertise required to meet the needs regardless of administrative homes. The success of these crosscutting efforts is based on diversity of expertise and experience, and more rigorous and efficient reviews.
2012 ABIG Accomplishments
Accomplishments during the year fall into several categories:
Reviews. Under ABIG’s direction, the Center continued to make progress in developing and implementing full life cycle risk-based approaches to the regulation of genetically engineered animals in three areas: GE animals for food production; GE animals that generate products such as drugs, biologics, or devices by GE animals for human biomedical use; and genetically engineered large animal models for human disease to supplement or replace mouse models. For these projects, the Group added experts from CVM’s Offices of New Animal Drug Evaluation (ONADE), Surveillance and Compliance (OSC), and Research (OR) – as well as experts from FDA centers that regulate human products, and from other government agencies.
Policy development. The Group continued work on development of policy positions on two key issues related to animal biotechnology. The first addressed the use of GE animals for production of animal and human medical products, such as biologics, biopharmaceuticals, and medical devices, which FDA regulates. ABIG took leadership during the year to identify the need for such a policy, and to recruit key technical and policy individuals from across the agency to prepare biopharm guidance for industry. The purpose of the guidance, which was in draft at the end of the fiscal year, will be to clarify how the agency intends to review the GE animals that produce these products. The guidance will provide recommendations as to how sponsors may prepare data and information for efficient use both by CVM (which regulates the GE animals) and the human product centers (which regulate the human use products produced by the GE animals). The goal of the effort is to help sponsors of both animal drug and human product applications to develop the data and information in support of their applications more efficiently, and to eliminate or significantly reduce duplicative reviews.
The second issue involved stem cells. A group member participated in the CVM-wide stem cell technology team’s work with the use of stem cells in veterinary regenerative medicine. We described the stem cell tech team’s efforts earlier in this report (see Advancing Regulatory Science and Innovation, page XX. As a part of the matrix-managed structure, this group member provides the stem cell technology team with broad-based expertise and experience in stem cell biology.
Inspections. It is an agency priority to improve its ability to perform effective, risk-based inspections. Emerging technologies, such as animal biotechnology, provide a particular challenge for inspection. Working closely with senior inspectors, members of ABIG carried out three inspections of three GE animal facilities in the U.S. and two foreign countries. Building on the inspectional experience, ABIG members and colleagues in the CVM Office of Surveillance and Compliance continue to work towards developing a compliance policy program. This program document will serve as a resource for agency personnel in the conduct of inspections related to GE animals.
ABIG continues to work with the Office of Research to develop and validate methods used to identify specific GE animals and products that come from them in order to ensure that only approved products enter commerce.
International Activities. Members of the group played key roles, representing the Center and agency in interactions with regulatory and scientific counterparts from other countries. Group members were especially active in the Organization of Economic Cooperation and Development (OECD). One group member led the U.S. delegation and chaired the OECD Task Force for the Safety of Novel Foods and Feeds in Paris in March 2012. The Task Force works toward the harmonization of approaches to the safety assessments of novel foods and feeds, including those derived from GE organisms and other new technologies. This harmonization activity requires close coordination within the Center and the agency, as well as with agencies across the U.S. government (EPA, USDA and other agencies concerned with agricultural biotechnology).
Two group members participated during the year in activities of the OECD Working Group for the Harmonization of Regulatory Oversight in Biotechnology. One group member co-chairs the drafting group for the Biology of Atlantic Salmon Consensus Document, while the other member (brought in from the Office of New Animal Drug Evaluation) is the lead author for the consensus document. The document is expected to progress to OECD review in 2013. As part of a joint delegation comprised of representatives from USDA’s Foreign Agricultural Service and CVM, two Group members visited the People’s Republic of China for an exchange of information on the state of research and development of GE livestock and fish. Group members led discussions with the Chinese delegations on the agency’s risk-based approaches to the regulation of GE animals. Members of the Chinese delegations discussed their research on GE animals, and gave an overview of the regulatory processes applicable to GE animals in China. The U.S. delegation also met with Chinese Academy of Sciences members from four institutions who are involved with GE animal research.
Outreach at national and international meetings. On behalf of CVM and the agency, members of the group engaged extensively in outreach to scientific and regulatory counterparts throughout the nation and the world, making presentations and otherwise participating in workshops and symposia. To illustrate the agency’s leadership in risk-based regulation of GE animals, several group members made formal presentations on risk-based approaches and emerging challenges in the regulation of GE animals.
Other Activities. Part of the group’s mandate is to identify and develop resources of utility to the entire Center and agency. One key example is a project that arose from the work of a summer intern veterinary student, who prepared an extensive searchable and hot-linked database of reportable animal disease as identified by the Centers for Disease Control, the USDA, and the World Organization of Animal Health. This database is available to the Center and other parts of the agency as an electronic resource. Other similar activities included working with students who developed resources that provide a compendium of methods that employ weight of evidence decision-making structures to be used as resources by the Center and agency.